The CA 1 neurons of the hippocampus have been shown to disappear by 4 days after 5 minutes of bilateral ischemia in the gerbil brain. The selective vulnerability of these neurons to short periods of ischemia provides an excellent model for the examination of the neurochemical events which precede neuronal death. In the initial study, metabolites were measured in the cell body layer of the CA 1 and CA 3 region of the hippocampus as well as in the cerebral cortex. The metabolites selected for measurement were associated with 1) energy metabolism, 2) glycolysis, 3) the GABA shunt and 4) synaptic transmisssion (i.e., cyclic nucleotides). The energy status, as reflected by the levels of ATP and P-creatine, was maintained from 1.5 to 48 hours of recirculation after which there was a drop but only in the affected region. The levels of glycogen and glucose were elevated during the early stages of recirculation, whereas those for lactate were somewhat depressed. These changes collectively suggest that there is a period of hypometabolism in all regions for up to 1 day of recirculation. By four days of recirculation, the glycolytic metaboliltes were significantly elevated but only in the CA 1 region which undoubtedly reflects the glial infiltration which occurs with the loss of the neurons. The levels of both GABA and glutamate decrease to varying degrees during recirculation, but as with the other metabolites the changes in the three regions are marked more by their similarities than their differences. Under normal circumstances, it is generally conceded that the metabolic rate of the brain is coupled to brain function; however, in various neurologic disorders it is possible that the functional status of the brain may be influenced by the perturbations in metabolism like those which occur during recirculation. The changes in GABA and glutamate provide some support for this possibility, since both are constituents of a major metabolic pathway and also serve as neurotransmitters. In addition, the delayed changes in the metabolites indicate that an effective post-traumatic treatment of stroke is a real possibility.